Molecular advances in pancreatic cancer: A genomic, proteomic and metabolomic approach

Table 1 Summary of molecular subtyping studies

Ref.	Subtypes	Clinical significance
	Genomic
Waddell et al[11]	Stable, locally re-arranged, scattered and unstable	High BRCA mutational signature in the unstable subtype, sensitizing to PARPi and PBC.
Singhi et al[12]	-	Real time genetic sequencing. 17% of specimens found to have sensitivities to available treatments. Potential therapeutic targets.
Aguirre et al[13]	SigA, SigB and SigC	Potential targets in 40% of patients. 48% eligible for trials/off-label use. Of 24% enrolled onto a clinical trial.
	Proteomic
Law et al[14]	Inflammatory, proliferative, progenitor-like and metabolic	↓Risk of death in metabolic and progenitor-like subtypes treated with FOLFIRINOX+Gemcitabine. ↑Survival in progenitor-like subtype treated with gemcitabine. SHMT1 a potential mediator of gemcitabine resistance.
Humphrey et al[15]	TKCC subtypes 1, 2 and 3	Subtypes 3 in both cohorts showed increased sensitivity to erlotinib, potentially mediated by tyrosine phosphorylation of RTK sites.
	ATCC subtypes 1, 2 and 3
	Metabolomic
Daemen et al[16]	Slow proliferating, glycolytic and lipogenic	Glycolytic subtype sensitive to inhibitors of aerobic glycolysis, glutaminolysis, γ-glutamylcysteine and Xct. Lipogenic subtype sensitive to lipid synthesis inhibitors.

BRCA; Breast cancer gene; RTK: Receptor tyrosine kinase; PBC: Platinum-based chemotherapy; PARPi: Poly (ADP-ribose) polymerase inhibitors; xCT: Cystine transporter; SHMT1: Serine hydroxymethyltransferase 1.

Table 2 Summary of biomarker discovery studies

Ref.	Biomarkers	Sensitivity	Specificity	AUC
Zhu et al[20]	ctDNA	0.64	0.92	0.9478
	CTC	0.74	0.83	0.8166
	Exosome	0.93	0.92	0.9819
Capello et al[23]	TIMP1, LRG1 and CA19-9	0.667/0.410	0.95/0.99	0.887
Mehta et al[26]	Panel of: Lactate, LysoPC (18:2), Alanine, Choline, Threonine, Asparagine, Tyrosine, Lysine, Palmitate and 3-hydroxybutyrate	-	-	0.992 vs NC
				0.957 vs T2DM
				0.653 vs CRC
		Biomarker + ve median survival		Biomarker - ve median survival
Peng et al[25]	Panel of: PZ, SHBG, VWF and CA19-9	19.2 mo		8.7 mo
			AUC
Martín-Blázquez et al[27]	Panel of: PS (12:0/15:1), TG (22:2/15:0/18:3), 4-oxo-Retinoic acid, Androsterone sulfate, LysoPE (18:2), Phenylalanylphenylalanine, all-trans-Decaprenyldiphosphate, LysoPC (18:2) and Dehydroepiandrosterone sulfate		0.992 (CI: 0.972-1.000)

ctDNA: Circulating tumour DNA; CTC: Circulating tumour cells; TIMP1: Metalloproteinase inhibitor 1; LRG1: Leucine rich alpha-2-glycoprotein 1; CA19-9: Carbohydrate antigen 19-9; CI: Confidence interval; NC: Normal control; T2DM: Type 2 Diabetes mellitus; CRC: Colorectal cancer.